Non‐osseous intradural tuberculoma of the thoracic spine with compressive myelopathy

Key Clinical Message An uncommon form of CNS tuberculosis called non‐osseous IDEM tuberculoma frequently results from paradoxical drug interactions. It should be considered one of the differentials when patients receiving ATT experience acute neurological impairment. Abstract Tuberculoma affecting the spinal cord is a rare condition in modern times. The occurrence of non‐osseous intradural tuberculosis, specifically in the spine, is even more exceptional. In fact, it is uncommon to encounter an intradural extramedullary tuberculous granuloma that lacks radiological indications of vertebral involvement, especially within the thoracic region. We present a case of a patient with a neurological deficit caused by a non‐osseous intradural tuberculoma in the thoracic region, without any associated bone involvement. The patient experienced a gradual deterioration of neurological function. An MRI of the thoracic spine revealed the presence of a tuberculoma located intradurally, extramedullary, and juxtamedullary of the T5 vertebra. The compression of the spinal cord resulted in paraparesis which was worsening to paraplegia. A D4–D6 laminectomy and microsurgical excision were performed under intraoperative neurophysiological monitoring (IONM), and the patient showed clinical recovery. Excellent clinical outcomes were achieved. However, it is crucial to consider the possibility of a non‐osseous intradural tuberculoma as a rare condition when encountering a SOL, particularly in patients with a history of tuberculosis and spinal cord compression. In cases where a progressing neurological deficit is present, a combination of surgical intervention and anti‐tuberculous treatment should be considered as the optimal approach.


| INTRODUCTION
Tuberculosis remains a significant global health burden, with central nervous system (CNS) involvement being a serious manifestation.The CNS involvement in developing countries constitutes nearly 10% of all tuberculosis patients. 1In the differential diagnosis of extensive spinal cord injuries, particularly in young patients with a history of pulmonary tuberculosis or tuberculous meningitis, it is important to consider the possibility of an intradural extramedullary tuberculoma. 2ere we will be discussing a case of intradural extramedullary tuberculosis of the thoracic spine, with progressive neurological dysfunction.4][5] The specific surgical technique employed depends on the location and extent of the tuberculoma.
Following surgery, anti-tubercular therapy is initiated to target the underlying tuberculosis infection.This typically involves a combination of multiple anti-tuberculosis medications, such as isoniazid, rifampicin, ethambutol, and pyrazinamide. 2The duration of anti-tubercular therapy may vary but generally lasts several months to ensure complete eradication of the infection.Concurrently, physiotherapy and rehabilitation assume significance in facilitating the functional restoration and enhancing the overall quality of life. 1 This report aims to discuss the diagnostic challenges, treatment strategy, and clinical outcomes, highlighting the importance of a multidisciplinary approach in managing this uncommon condition.

| CASE REPORT
A 29-year-old man, who had been under treatment for disseminated tuberculosis for 7 months, was admitted with progressive weakness of both lower limbs leading to difficulty in walking.There was no history of fever, cough, palpitations, or breathlessness.Physical examination revealed a palpable spleen but no lymphadenopathy.He had spastic paraparesis with involvement in right side more than the left.There was severe girdle pain at T5 level.The patient underwent a computed tomography (CT) chest, which revealed multiple patchy resolving ground glass opacities and interlobular septal thickening in bilateral lower lobes, predominantly superior and posterior basal segments, suggesting resolving tuberculosis.Also, mild centrilobular emphysema in bilateral upper lobes with sub-centimeter right paratracheal and left paraaortic lymph nodes, the largest measuring 7 mm, were present.
Other findings included splenomegaly measuring 17.6 cm and calcified hepatic granulomas (segment VII).
Magnetic Resonance Imaging (MRI) thoracic spine revealed a single 2.1 × 1.7 × 1.45 cm intradural/juxtamedullary and extramedullary mass appearing as well-defined T1-weighted low signal/T2-weighted FLAIR bright signal with central necrosis and marginal enhancement after gadolinium (Gd) suggestive of immature tuberculoma at T5 level with surrounding edema (Figure 1A-C).
No evidence of vertebral TB, spinal tract infiltration, or engulfment was noted.A diagnosis of D5 intradural extramedullary space-occupying lesion (SOL) with spastic paresis, cord compression, compressive myelopathy, disseminated tuberculosis, and post-tuberculous medication-induced hepatic granuloma was made.D4-D6 laminectomy and microsurgical excision under IONM were planned to remove the lesion.After pre-anesthetic assessment and consent, the patient underwent the procedure with the head held in a horseshoe, subperiosteal muscle dissection made, and laminae exposed.Durotomy was performed under a microscope, and the lesion was visualized.A grayish-white, firm lesion with a central necrotic area was exposed (Figure 2).
The pus was aspirated, followed by internal bulking using ultrasonic surgical aspirator (Figures 3-5).The thin rim of the capsule was left behind but was coagulated well.Homeostasis was achieved, and the dura was closed using a 5-0 proline continuous suture.The patient tolerated the procedure well.After surgery, he was treated with antibiotics, anti-diabetics, steroids, anti-tubercular drugs, anti-inflammatory, gastroprotectives, antiemetics, and other supportive measures.Physiotherapy measures were instituted.The neurologist was involved in his paraparesis care, and an endocrinologist for glycemic control.He gradually improved symptomatically, able to walk with minimal support.

| DISCUSSION
Tuberculosis (TB) remains a common health issue in developing countries, even though TB has not been seen widely as before. 6Osseous TB involvement may account for up to 35% of patients with extrapulmonary TB, and vertebral osteomyelitis infections (Pott's disease) account for 25%-60% of all osseous infections caused by TB. [7][8][9] Approximately 10% of patients with extrapulmonary tuberculosis experience CNS involvement, typically resulting from the bacteremic stage of the disease.During this stage, tuberculous lesions known as Rich foci may develop in the meninges or within the brain or spinal cord tissue. 10,11After several months or even years, these foci can rupture into the cerebrospinal fluid, leading to meningitis, or they can enlarge and form tuberculomas within the brain or spinal cord parenchyma.
The pathogenesis of central nervous system tuberculosis involves the development of small foci of tuberculosis, known as rich foci, in the brain, spinal cord, or meninges. 10Earlier studies by Rich and McCordock showed that TBM requires direct inoculation of the bacilli through a meningeal focus in the central nervous system.However, later studies showed that disseminated tuberculosis plays a crucial role in the development of tuberculosis. 12Tumor necrosis factor alpha (TNF-α) is a critical cytokine in  M. tuberculosis neuropathogenesis.Although it helps in granuloma formation and control of mycobacterial infections, local production of TNF-α in the central nervous system can alter the permeability of the blood-brain barrier and promote the progression of TBM. 13 Human microglia are selectively infected by M. tuberculosis, and the CD14 receptor facilitates engulfment of unopsonized bacilli by microglia.Microglia infected with M. tuberculosis produce a variety of cytokines and chemokines, including TNF-α, IL-6, IL-1β, CCL2, CCL5, and CXCL10.Microglia play a central role in the neuropathogenesis of tuberculosis, and their infection can lead to immunosuppressive effects, especially in more virulent strains. 14imilarly, among various forms of spinal TB involvement, such as Pott disease, non-osseous spinal TB, tuberculous spinal meningitis, and tuberculous arachnoiditis, non-osseous spinal tuberculoma is infrequent.6][17] Non-osseous spinal tuberculomas typically originate from a primary pulmonary focus, spreading hematogenously or through direct extension from hilar lymph nodes. 18In our case, a rare and unexpected involvement occurred in the form of a non-osseous IDEM tuberculoma of the spinal cord, resulting in paraparesis despite the patient receiving anti-tubercular therapy (ATT).To our knowledge, this is the first reported case of a tuberculoma at the juxtamedullary location in the thoracic region.
The clinical presentation of the case aligns with the findings reported in the literature, which often show a higher prevalence among males. 19The most common presentation in our case was spastic paraplegia, post-ATT liver failure, and respiratory problems associated with tuberculosis and COVID-19.Nevertheless, tuberculomas are slow growing with areas of necrosis that are encapsulated, avascular, and infrequently calcification.Our patient exhibited involvement of the thoracic spinal cord, which aligns with the reported incidence of up to 70% of cases in the literature.The thoracic spine is the most frequently affected site in Pott's syndrome. 20he radiological imaging findings of tuberculomas can vary depending on the stage of the lesion.On MRI, tuberculomas may present with noncaseating granulomas or caseating granulomas characterized by a solid or liquid center. 21The tuberculous lesion typically appears isointense on T1W images, isointense to hypointense on T2Wimages, and exhibits ring enhancement with a hypointense center on gadolinium-enhanced MR scans.][24] A combination of surgical intervention and medical treatment has shown excellent outcomes.8][29][30][31][32][33] The reason for the poor response to chemotherapy in this condition remains unclear.Therefore, we believe that surgery is warranted when intradural extramedullary spinal tuberculoma arises as a paradoxical response to therapy.
The list of similar published cases is mentioned in Table 1.

| CONCLUSIONS
IDEM tuberculoma is a rare manifestation of CNS tuberculosis, often arising as a result of paradoxical reactions to anti-tubercular medication.When patients on anti-tubercular therapy develop new-onset neurological deficits indicative of compressive myelopathy, IDEM tuberculoma should be considered as one of the potential causes.Early and accurate diagnosis, along with timely initiation of appropriate medical or surgical interventions, is crucial to prevent irreversible dysfunction.Excision plays a pivotal role in the treatment of this uncommon condition.

F
I G U R E 1 The MRI images of the thoracic spine.(A) Coronal T1-weighted MRI image shows a ring-like enhancing intradural lesion after gadolinium.(B) Sagittal T1-weighted MRI image shows a 2.1 × 1.7 × 1.45 cm intradural/juxtamedullary and extramedullary mass with central necrosis and marginal enhancement after gadolinium suggestive of immature tuberculoma at T5 level.(C) Axial T2-weighted image.F I G U R E 2 The capsule and necrotic component is seen which is densely adherent to spinal cord.F I G U R E 3 Intraoperative picture showing a densely adherent lesion with neovascularization.F I G U R E 4The capsule is incised, and pus is delivered off the lesion.F I G U R E 5Post-excision status with decompression of the spinal cord.
List of case reports having similar presentation.
T A B L E 1